Although rheumatoid factor (RF) is associated with rheumatic diseases and is generally considered a pathological autoimmune response, we have recently shown an IgM class RF to be protective against Trypanosoma lewisi in rats. RF was found to be the factor in the serum of never-infected, lactating rats which would specifically agglutinate one stage of the parasite, the IgG coated "adult" stage. This activity explained the aborted "adult" phase of infection in these rats. RF activity was found in rat milk and to some extent in suckling pup serum where the "adult" phase of parasitemia is also selectively suppressed. These data infer transfer of protection from dam to pup via milk. In addition to the lactation associated RF, RF is induced by IgG coated "adult" parasites in non-lactating rats during the usual course of infection causing termination of their parasitemia. Strong circumstantial evidence indicates that a similar mechanism operates in T. cruzi infections, a parasite of great medical importance. We have thus described an entirely new function for rheumatoid factor and a new immune mechanism of parasite control. A specific female function, lactation, is associated with this RF induction and this may relate to the more common occurrence of RF and rheumatic disease in females. As first steps in extending our observations we propose to: 1) Clarify the specificity of this RF; 2) Study its apparent transport across the rat pup intestine; 3) Confirm our model of the immune response to T. lewisi (that there is no antigenic variation and a blocking antibody serves as antigen for a RF) by analysis of parasite antigens and antibody production via crossed immunoelectrophoresis. The finding will be confirmed by supplying specific antibodies to irradiated, infected rats to reproduce the normal immune response and course of infection.